Aricept‐induced Nightmares in Alzheimer's Disease: 2 Case Reports

To the Editor: Donepezil (Aricept), a medication newly approved by the FDA, is reported to have no significantly higher side effect profiles than placebo.1 This compound works by inhibiting cholinesterase in the central nervous system, thereby increasing the available neurotransmitter, acetylcholine, for improved synaptic communication.2 In published preclinical studies, donepezil has been reported to display a high affinity for selective acetylcholinesterase inhibition in the central nervous system.3 We recently administered Aricept to two patients, both of whom experienced nightmares that required changing the dosing from the recommended nighttime administration to morning dosing. In both cases the nightmares did not recur. In Case One, an 84-year-old patient, diagnosed with probable Alzheimer's disease using the DSM-IV and NINCDS-ADRDA criteria, global deterioration scale of 4, with a Mini-Mental Status Examination score of 20, was prescribed 5 mg of Aricept to be given at bedtime. After 1 week, the patient was brought back to the office for a routine follow-up. The patient offered no new complaints or concerns, but his wife noted increasing problems with his sleep. Whereas previously he had had no insomnia, she noted in the past week he would awake frequently and appear frightened. When she questioned him further, he responded that he had had horrible dreams, but he could not elaborate any further. This occurred each night. She was instructed to stop the Aricept for 1 week and report on his sleep patterns. No nocturnal awakenings were noted. The patient was then rechallenged for 2 nights, and each night he awoke several times in a terrorized state. The family was instructed to stop dispensing the medication at night and to administer the Aricept in the morning. No further sleep problems were noted during the subsequent 2 months. In Case Two, a 77-year-old woman diagnosed with probable Alzheimer's disease using the DSM-IV and NINCDS-ADRDA criteria, global deterioration scale of 5, with a Mini-Mental Status Examination score of 14, was prescribed 5 mg of Aricept to be given at bedtime. She had no history of sleep problems. Three days later the husband called, very upset that his wife was screaming in the middle of the night for no apparent reason. With the previous case as a possible explanation for her nighttime agitation, we asked him to hold the medication for 1 week. No nocturnal awakenings were noted. She was rechallenged for 3 days, with Aricept given at bedtime, and each evening she awakened in a state of terror. We suggested dosing in the morning, and during the next 3 weeks, no such nocturnal problems were reported. Donepezil appears to be a very safe medication when used in selected patients with mild to moderate Alzheimer's disease. Patients with Mini-Mental Status Examinations scores ranging from 10 to 24 were those found to benefit most from this medication. Nightmares are not a reported complication of Aricept therapy. We feel this adverse effect of Aricept is likely not uncommon and can be treated easily. By administering the Aricept in the morning to all patients who suffer such a condition, subsequent insomnia might be significantly reduced or eliminated. We suggest prescribing physicians be made aware and that the manufacturer alert the physicians in the medical community to this complication of Aricept therapy.